The sites of synthesis and mode of intracellular assembly of the procollagen molecule will be studied in cultured human fibroblasts. The enzymatic reaction that converts procollagen to tropocollagen will be examined in detail. A radioimmune assay for procollagen will be developed with the view of measuring collagen turnover in human diseases. Cultured fibroblasts from patients with Marfan's syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta will be studied with respect to the structure and metabolism of the procollagen synthesized and the structure of the cross-linking regions of the tropocollagen formed. These studies could establish the molecular bases of these inherited disorders and provide the means for genetic screening.